The motivation for this research proposal derives from the recently reported increased incidence of hematologic toxicity in patients on 5-fluorocytosine (5-FC), and the fact that the manifestations of toxicity are similar to those seen with 5-fluorouracil (5-FU). A preliminary study using a gas chromatography-mass spectrometry technique has demonstrated for the first time that 5-fluorouracil is formed in patients receiving oral 5-fluorocytosine. The level of 5-FU found in the serum of a limited number of 5-FC treated patients who had developed toxicity was felt to be significantly elevated (greater than 1 ug/ml), particularly when compared with the level of 5-FU found in cancer patients receiving oral 5-FU. It is proposed that an experimental model will be developed using two species: 1) rat -- an animal which has a relatively high LD50 for 5-FC, but in which metabolites of 5-FU have previously been noted, and 2) rabbit -- an animal which has a relatively low LD50 for 5-FC and 5-FU levels will be closely monitored by analytic methods in animals receiving 5-FU alone, as well as in animals receiving 5-FU and Amphotericin-B. White blood count will be monitored over an estimated 2 month course, along with serum creatinine. The studies will attempt to determine whether a correlation exists between 5-FU levels and hematoxicity. An additional major questions to be asked in the experimental model is whether the intestinal microflora determines deamination of 5-FC to 5-FU. Methods of reducing 5-FU toxicity and increasing 5-FC therapeutic effectiveness will be evaluated. Throughout the 3 year period of this study, patients who are receiving 5-FC at the Medical College of Virginia Hospitals, will be monitored prospectively for both 5-FC and 5-FU at twice weekly intervals. An attempt will be made to study 5-FU pharmacokinetics closely particularly in the high risk setting of renal dysfunction to determine the relative importance of 5-FU as a predictor of toxicity.